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Apolipoprotein Measurement Improve Myocardial Risk Assessment

Measurement of apolipoproteins could be a better indicator of myocardial risk than presently accepted cholesterol measurements.

"Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB (Apolipoprotein B), apoB/apoA-I (apolipoprotein A-I), and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk, " declares Dr Goran Walldius and colleagues at the Karolinska Institute and AstraZeneca, Stockholm, Sweden.

A major aim of the study was to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol.

Dr Walldius and colleagues note that hypercholesterolemia, high concentrations of LDL-cholesterol in particular, is generally accepted as one of the strongest risk factors for atherosclerotic cardiovascular disease and mortality, at least in individuals under the age of 70. Hypertriglyceridaemia, although generally associated with low HDL-cholesterol, is recognized as an independent risk factor for atherosclerosis.

"Results of several studies have suggested that apolipoprotein B (apoB) in atherogenic particles - mainly LDL, but also VLDL, intermediate density lipoprotein, and lipoprotein (a) and apolipoprotein A-I (apoA-I) in anti-atherogenic particles, such as HDL types, could improve the prediction of risk of coronary artery disease," the investigators add. "Early prospective studies with apolipoproteins yielded mixed results, because methods, procedures, and population-based reference values were not standardized."

Researchers recruited 175,553 men and women, most of whom had taken part in screening programs, who were measured for concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was calculated.

The researchers examined data at a mean follow-up of 66.8 months for 98,722 men and 64.4 months (41.4) for 76,831 women. They found that 864 men and 359 women had had fatal myocardial infarction.

Univariate analyses adjusted for age, and multivariate analyses adjusted for age, total cholesterol, and triglycerides, found the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. There was a protective effect from ApoA-I. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes.

"Our results show that increasing concentrations of apoB and LDL-cholesterol are related to a greater risk of fatal myocardial infarction, whereas HDL-cholesterol and apoA-I are both negatively related to risk," the researchers declared. "The numerically steepest increase in risk was obtained for the ratio apoB/apoA-I, which increased about 3.8-fold in men, when the risk for those in the highest quartiles was compared with those in the lowest quartiles."

Dr Walldius and colleagues conclude: "We realize that LDL-cholesterol and HDL-cholesterol are the recommended lipid variables in international guidelines for treatment, on the basis of evidence obtained over many years from epidemiological and trial data. However, new information shows the importance of apoB and apoA-I as risk predictors, which may be of great value for an individual.

"Therefore, we suggest that prediction of future cardiac death could be improved by measurement of apoB, apoA-I, and the apoB/apoA-I ratio. These measurements could show which individuals are at the highest or lowest risk of fatal myocardial infarction at all lipid concentrations, and could therefore be useful in clinical practice in assessment of risk and decisions about lipid-lowering treatment."

In addition, ApoB and apoA-I could be of greatest value for diagnosis and treatment in individuals who have common lipid abnormalities, "but have normal or low LDL cholesterol concentrations. We hope that new guidelines will consider the value of apoB and apoA-I in future clinical practice."
Lancet 2001; 358: 2026-33.

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